Bullous Pemphigoid Disease Area Index Research Articles

Diacron-Reactive Oxygen Metabolites Levels Are Initially Elevated in Patients with Bullous Pemphigoid

Reactive oxygen species (ROS) are involved in the pathogenesis of bullous pemphigoid (BP), but this involvement has not been fully elucidated. In this study, to further elucidate the pathogenic role of ROS in BP, we examined the results of the diacron-reactive oxygen metabolite (d-ROMs) test and the biological antioxidant potential test for 16 BP patients who visited our hospital before being treated with systemic corticosteroids. In the BP patients, the average d-ROMs levels, expressed in Carratelli units (U.CARR), were significantly reduced at 1 month of treatment (from 335.6 ± 40.3 U.CARR to 224.7 ± 61.6 U.CARR, P<0.001). Bullous Pemphigoid Disease Area Index (erosions/blisters) scores correlated with d-ROMs levels (r=0.51), suggesting that those levels reflect the disease severity. We also performed staining of 3,5-dibromotyrosine (DiBrY) in skin tissues. DiBrY is expected to be a marker of tissue damage related to inflammation and allergies. The DiBrY was stained in infiltrated cells around the dermis, throughout the blister fluid, and at the basement membrane within the blister. It is considered that tissue destruction caused by the myeloperoxidase released from neutrophils and by eosinophil peroxidase released from eosinophils is involved in blister formation. The results suggest that ROS play a role in BP.

IgE anti-BP180 NC16A autoantibody in both serum and blister fluid samples does not correlate with disease activity of bullous pemphigoid.

The correlation between IgE anti-BP180 NC16A autoantibody and disease activity of bullous pemphigoid (BP) remains disputable. To determine the levels of IgE anti-BP180 NC16A autoantibody and its clinical significance in untreated BP patients. IgG and IgE anti-BP180 NC16A autoantibody in serum and blister fluid samples of 34 untreated BP patients was detected by enzyme-linked immunosorbent assay (ELISA), and correlation with clinical and pathological features of BP were statistically analysed. The Bullous Pemphigoid Disease Area Index (BPDAI) was used to measure disease activity of BP. The mean baseline level of IgG anti-BP180 NC16A autoantibody in serum and blister fluid samples of untreated BP patients was 75.3U/mL and 1.54U/mL, respectively (A450, cutoff: 0.126). IgE anti-BP180 NC16A autoantibody was positive in 21.9% serum and 14.7% blister fluid samples of untreated BP patients. IgE anti-BP180 NC16A autoantibody levels in serum samples positively correlated with those from blister fluid samples (r = 0.983, p < 0.05). However, IgE anti-BP180 NC16A autoantibody level in both serum and blister fluid samples of untreated BP patients did not correlate with IgG anti-BP180 NC16A autoantibody, age, extent of elevated peripheral blood eosinophils, BPDAI erosion/blister score, BPDAI urticaria/erythema score, BPDAI pruritus score, BPDAI without damage score, or BPDAI total score (all p > 0.05). No significant correlation was identified between disease activity and positive or negative anti-BP180 NC16A IgE autoantibody. Conclusion: IgE anti-BP180 NC16A autoantibody in both serum and blister fluid samples does not appear to correlate with disease activity of BP.

Long-term efficacy and safety of dupilumab for severe bullous pemphigoid: A prospective cohort study

BackgroundBullous pemphigoid (BP) is a common subepidermal bullous disease. Dupilumab is a novel treatment for BP. However, its long-term efficacy and safety have not been demonstrated in prospective studies. ObjectiveEvaluate the long-term efficacy and safety of dupilumab in treating severe BP. MethodsPatients were divided into two groups: the methylprednisolone monotherapy group (M), and the methylprednisolone and dupilumab combination therapy group (D + M). This study consisted of two stages. The first stage focused on the initial treatment phase, where the early efficacy and safety was evaluated. The study then entered the 12-month maintenance treatment stage, where we assessed recurrence in both groups. Additionally, we evaluated the rate of healing of skin lesions, glucocorticoids burden and length of hospital stay and various laboratory test indicators. ResultsAfter four weeks of treatment, the Bullous Pemphigoid Disease Area Index (BPDAI) and pruritus Numerical Rating Scale scores of the D + M group decreased significantly more than those of the M group. The median BPDAI at week 4 was 0 (range: 0.0–3.0) in the D + M group and 10.0 (5.0–12.0) in the M group (P < 0.001). Patients treated with dupilumab experienced a faster cessation of new blisters, quicker glucocorticoid reduction, shorter healing times, and shorter hospital stays (P < 0.001). Additionally, after two weeks of treatment, the levels of eosinophils and immunoglobulin E also decreased (P < 0.001). Follow-up studies further demonstrated that dupilumab monotherapy was associated with a lower recurrence rate. Notably, no serious adverse effects were observed in the study. ConclusionsOur study provides evidence for the efficacy of dupilumab in the treatment of BP based on prospective studies. Additionally, our findings suggest that dupilumab can be considered a reliable single-agent maintenance treatment due to its good safety profile and lower relapse.

Evaluation of Dupilumab in Patients With Bullous Pemphigoid

Dupilumab is a theoretically novel therapy for bullous pemphigoid (BP). However, its effectiveness and safety have yet to be confirmed in a large-scale study. To assess the efficacy and safety of dupilumab in patients with BP and evaluate factors that potentially affect short-term and long-term outcomes. A retrospective cohort study was conducted from January 1, 2021, to July 31, 2022. The median (IQR) follow-up period was 24.6 (11.5-38.4) weeks. This multicenter study was performed in 6 dermatology departments of the National Autoimmune Bullous Diseases Cooperative Group of China. Adult patients with BP that received 300 mg of dupilumab every 2 weeks following an initial dose of 600 mg were included. Patients were eligible if they had a clinical presentation of BP combined with immunological or pathological evidence. Patients with drug-induced BP, with less than 4 weeks of follow-up, and who received dupilumab or any other biologics within 6 months were excluded. The primary outcome was the proportion of patients who achieved disease control within 4 weeks. Disease control was defined as the absence of new lesions and pruritus, combined with the healing of existing lesions. Complete remission rates, relapse rates, changes in Bullous Pemphigoid Disease Area Index (BPDAI) scores, itching numerical rating scale (NRS) scores, laboratory results within 64 weeks, and adverse events (AEs) were also assessed. Among 146 patients (median [IQR] age, 73 [64-85] years; 86 [58.9%] male patients) included in the study, 127 (87.0%) patients achieved disease control within 4 weeks, with a median (IQR) time of 14 (7-14) days. A total of 52 (35.6%) patients achieved complete remission, and 13 (8.9%) patients relapsed during the observation period. The complete remission rate and cumulative relapse rate at week 64 were 62.5% (5 of 8) and 30.9%, respectively. There was rapid and sustained improvement in clinical indicators and laboratory examination results after dupilumab treatment, including BPDAI scores, itching NRS scores, serum anti-BP180 and anti-BP230 antibodies, total IgE levels, and eosinophil count. Of these 146 patients, 107 (73.3%) did not report any AEs. The most common AEs were infections and eosinophilia. Serum anti-BP180 antibody levels of greater than 50 relative units (RU)/mL (OR, 3.63; 95% CI, 0.97-12.61; P = .045) were associated with 4-week disease control, and male patients were more likely to relapse (HR, 10.97; 95% CI, 1.42-84.92; P = .02). In this retrospective cohort study, dupilumab treatment was associated with improved clinical symptoms in patients with BP. The safety profile was favorable, although concurrent infection and eosinophilia might pose potential concerns. This study suggests that patients with anti-BP180 antibody levels of at least 50 RU/mL and female sex may respond better.

Dietary habits in Japanese patients with bullous pemphigoid: low intake of retinol.

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease. Dietary habits may modulate the pathogenesis of BP. We evaluated dietary habits in Japanese patients with BP and compared their results to those of age- and sex-matched healthy controls. We also examined the relationship between dietary habits versus IgG anti-BP180NC16A antibody or parameters of BP disease area index (BPDAI); cutaneous blisters/erosions, cutaneous urticaria/erythema, and mucosal blisters/erosions. Dietary habits were assessed by the validated, Brief-type self-administered Diet History Questionnaire. Severity of disease was assessed with BPDAI. Patients with BP showed a lower intake of retinol (vitamin A1) and beverages, and a higher intake of seasoning/spices, compared to controls. The bivariate and multivariable logistic regression analysis showed that BP was associated with a low intake of retinol and beverages. There were no significant correlations between IgG anti-BP180NC16A antibody levels and intake of nutrients/foods. The BPDAI score for cutaneous blisters/erosions significantly positively correlated with intake of carbohydrate and negatively with intake of retinol, vitamin A, animal fat, cholesterol, phosphorus, and vitamin B2. The BPDAI score for cutaneous urticaria/erythema significantly negatively correlated with intake of vitamin A. BP patients with mucosal blisters/erosions had a higher intake of cholesterol, n-6 polyunsaturated fatty acid, and eggs, and lower intake of seasoning/spices, compared to patients without BP. The supplementation of vitamin A might have prophylactic and/or therapeutic effects on BP.

Analysis of IL-10 and IL-35 in dipeptidyl peptidase-4 inhibitor-related bullous pemphigoid.

The association between immunoregulatory cytokines, such as interleukin (IL)-10 or IL-35, and dipeptidyl peptidase-4 inhibitor (DPP4i)-related bullous pemphigoid (BP) has not been evaluated. Serum IL-10 and IL-35 levels were measured in 39 patients with BP (24 males and 15 females; 6 DPP4i-related and 33 DPP4i-unrelated BP patients) and 10 healthy controls. The number of CD26+ cells in the dermis around bulla on sections was counted immunohistochemically for 12 patients (six patients with DPP4i-related BP and six randomly sampled patients with DPP4i-unrelated BP). Patients with DPP4i-related BP had lower levels of serum eosinophils (DPP4i-related vs. DPP4i-unrelated BP: 476.1 ± 234.0 vs. 911.3 ± 948.8/μL; p = 0.537) and a higher rate of infiltrating CD26+ cells (32.9 ± 7.1% vs. 15.7 ± 4.4%; p = 0.01). There were no significant differences in serum IL-10 (6.77 ± 0.24 vs. 6.84 ± 0.20 pg/mL), serum IL-35 (2.63 ± 0.17 vs. 2.63 ± 0.21 pg/mL), serum anti-BP180NC16a antibodies (67.31 ± 37.4 vs. 76.18 ± 54.59 U/mL) and Bullous Pemphigoid Disease Area Index before treatment in this study. Serum IL-10 and IL-35 levels do not increase in patients with BP and may not be a candidate for a therapeutic target for BP. An increase in CD26+ cells might be associated with DPP4i-related BP.

Clinical Phenotypes and the Clinical Course of Bullous Pemphigoid Receiving Dipeptidyl Pepitidase-4 Inhibitor Treatment: An Analysis of Cases in a Single Japanese Center.

Objective Several studies have shown an increased risk of bullous pemphigoid (BP) when receiving dipeptidyl pepitidase-4 inhibitor (DPP-4i) treatment. The present study explored the associations of DPP-4i treatment with the clinical phenotypes and clinical course of BP. Methods We analyzed data of 146 patients with BP at Tokai University School of Medicine from December 1, 2009, to December 31, 2021. We obtained data by a retrospective medical record review and compared the bullous pemphigoid disease area index (BPDAI) between diabetes patients receiving DPP-4i treatment and those not receiving DPP-4i treatment. We employed multivariable linear regression models to explore the association between the DPP-4i treatment and the BPDAI scores. Results Among 53 BP patients with diabetes, 33 had developed BP during treatment with DPP-4i agents, among which vildagliptin was the most frequently used. The urticaria/erythema scores of the BPDAI were significantly lower in patients who developed BP while receiving DPP-4i treatment than among others. Of note, 69.2% of the patients who stopped DPP-4i treatment experienced complete remission, and the clinical course was more favorable in patients with lower scores for urticaria/erythema than among others. Conclusion These findings suggest that, in patients who developed BP while receiving DPP-4i treatment, a noninflammatory phenotype may indicate a high likelihood that DPP-4i treatment contributes to the development of BP. The discontinuation of DPP-4i should be carefully considered in close consultation with dermatologists.

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio are positively correlated with disease activity of bullous pemphigoid.

Bullous pemphigoid (BP) is a complex inflammatory process with elevated levels of autoantibodies, eosinophils, neutrophils, and various cytokines. Hematological inflammatory biomarkers can reflect inflammatory state in various diseases. Up to now, the correlations of hematological inflammatory biomarkers and disease activity of BP remain unknown. The purpose of this study was to clarify the associations between hematological inflammatory biomarkers and disease activity of BP. The levels of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), platelet-to-neutrophil ratio (PNR) and mean platelet volume (MPV) of 36 untreated BP patients and 45 age and gender matched healthy controls were detected by routine blood tests. The correlations between hematological inflammatory markers and clinical characteristics of BP were statistically analyzed. The Bullous Pemphigoid Disease Area Index (BPDAI) was used to measure disease activity of BP. The mean levels of NLR, PLR, PNR and MPV in 36 untreated BP patients were 3.9, 157.9, 45.7 and 9.4fl, respectively. Increased NLR (p < 0.001), PLR (p < 0.01), and MPV (p < 0.001) but decreased PNR (p < 0.001) were observed in BP patients when compared with healthy controls. In BP patients, the levels of NLR were positively correlated to BPDAI Erosion/Blister Scores (p < 0.01); and the levels of NLR and PLR were both positively correlated to BPDAI without Damage Score (both p < 0.05) and BPDAI Total Score (both p < 0.05). No correlation was found in other statistical analyses between hematological inflammatory markers and clinical characteristics in BP patients involved in the present study. Therefore, NLR and PLR are positively correlated with disease activity of BP.

The Importance of Patient-Focused Drug Development in Pemphigus and Pemphigoid

The Importance of Patient-Focused Drug Development in Pemphigus and Pemphigoid

Interleukin-36 cytokines are overexpressed in the skin and sera of patients with bullous pemphigoid.

Bullous pemphigoid (BP) is an autoimmune bullous disease, characterized by autoantibodies targeting BP180 and BP230. The role of interleukin (IL)-36, a potent chemoattractant for granulocytes, in BP remains elusive.The expression of IL-36 cytokines (IL-36α, β, γ) and their antagonists (IL-36Ra and IL-38) was analysed in the skin and serum samples of patients with BP (n= 31), psoriasis (n= 10) and healthy controls (HC) (n= 14) by quantitative polymerase chain reaction and enzyme linked immunosorbent assay, respectively. Skin and serum levels of all cytokines were correlated with the Bullous Pemphigoid Disease Area Index (BPDAI) score and with the serum concentration of pathogenic antibodies.IL-36α, IL-36β, IL-36γ and IL-36Ra were significantly (p< 0.05) overexpressed in BP skin compared to HC, without remarkable differences relative to psoriasis skin. The expression of IL-38 was significantly (p< 0.05) higher in BP compared to psoriasis skin.IL-36α and γ, but not β, serum concentrations were significantly (p< 0.05) higher in BP compared to HC. IL-36γ was significantly (p< 0.05) more expressed in the serum of psoriasis patients than BP. The serum concentration of IL-36Ra and IL-38 were similar between BP and HC, while IL-38 serum levels were significantly (p< 0.05) higher in BP compared to psoriasis patients. Serum IL-36α correlated significantly with BPDAI (r= 0.5 p= 0.001).IL-36 agonists are increased in BP patients, both locally and systemically. Serum IL-36α might represent a potential biomarker for BP. An inefficient balance between IL-36 agonists and antagonists is likely to occur during BP inflammation.

Brain MRI findings in patients with bullous pemphigoid: A case-control study.

Evidence suggests that bullous pemphigoid (BP) is associated with multiple neurological disorders. We aimed to compare brain magnetic resonance (MRI) findings between BP patients and a control group. This case-control study included patients with BP referred to two dermatology clinics during a two-year period. A group of individuals attending the same clinics for cosmetic procedures were selected as controls. First, participants' general information including age, gender, education, weight and underlying disease was recorded. For BP patients, the drugs and the BP Disease Area Index (BPDAI) were recorded as well. Then, all participants underwent brain MRI without contrast. The Fazekas scale, the general cerebral atrophy (GCA) score, and the Medial Temporal lobe Atrophy (MTA) score were used to assess MRI images. Overall, 24 BP patients and 24 controls were evaluated in this study. Both groups were comparable regarding age, gender and education. However, diabetes and hypertension were more frequent in the control group. The mean BPDAI total score was 51.39 ± 68.92 in BP patients and most of them used rituximab (41.7%). None of the participants had MS or Alzheimer MRI patterns. There was no difference between groups in terms of GCA and MTA scores. Furthermore, the frequency of partially empty sella did not differ significantly between BP patients and controls (p= 0.461); nevertheless, grade-3 Fazekas was significantly higher in BP patients compared to controls (25% vs. 0%, p= 0.019). Of note, one BP patient had an epidermoid cyst and another had moderate enlargement of three ventricles. Also, new infarcts were observed in two and old infarcts in four BP patients. Although the majority of abnormal brain MRI findings were more frequent in BP patients compared to controls, only grade-3 Fazekas was significantly higher and acute infarcts were exclusively observed in BP patients.

Rituximab Therapy for Persistent, Severe and Extensive Idiopathic Bullous Pemphigoid

Background: Idiopathic Bullous Pemphigoid (IBP) is a rare blistering autoimmune disease. Its morbidity and mortality have remained high owing to complications of extensive skin involvement as well as its conventional steroid therapy. We reviewed the medical literature and found indicators of an autoimmune etiology for its pathogenesis triggering genetically predisposed patients. Objective: to evaluate, prospectively, the role of Rituximab (R) therapy in its persistent, severe and extensive form. Patients and methods: A total of 12 patients, with disease duration of 6 ± 1 months, were treated with yearly R infusions (1 g followed by 1 g 2 weeks later). Results: Significant clinical improvement was achieved as documented by decrease in total score of Bullous Pemphigoid Disease Area Index from 60 ± 3 to 6 ± 2 that persisted for 26 ± 11 months of follow up. Moreover, IBP autoantibodies (anti-BP 180 and anti-320 IgG) levels fell from to 91 ± 3 and 81 ± 2 to 8 ± 2 and 9 ± 2, respectively. Conclusions: R is a safe and effective treatment for severe IBP and such response further confirms its autoimmune pathogenesis.

Intravenous immunoglobulin in patients with bullous pemphigoid insufficient response to corticosteroids: Nationwide post-marketing surveillance in Japan

BackgroundIn Japan, intravenous immunoglobulin (IVIG) has been approved for corticosteroid-unresponsive bullous pemphigoid (BP); however, its usage, efficacy, and safety in clinical settings remain unclear. ObjectiveTo elucidate IVIG efficacy, we examined the improvement in disease severity based on the Bullous Pemphigoid Disease Area Index (BPDAI). MethodsIn this 3-year (April 2016–March 2019), prospective, post-marketing, observational surveillance study, we enrolled 379 patients (51.3 % men; mean age, 74.5 years) with corticosteroid-unresponsive BP treated with IVIG from 143 institutions in Japan (720 treatment cycles). The percentage of patients who improved by at least one severity stage or whose symptoms completely resolved based on the BPDAI score was evaluated at 15, 30, and 60–90 days. ResultsThe improvement rates at 15, 30, and 60–90 days after initial treatment in the 328 IVIG-naïve patients were 70.7 %, 83.5 %, and 84.3 %, respectively. The BPDAI score decreased rapidly and significantly by 15 days compared with that observed during pre-treatment. Further improvement was observed at 30 and 60–90 days. The corticosteroid dose and anti-BP180 antibody titers decreased significantly post-treatment (both, p < .001). Approximately 25 % of IVIG-naïve patients underwent multiple treatment cycles. The improvement rate at 30 days after the final dose was 88 %, and the symptoms completely resolved in 44 % of patients. The incidence of adverse drug reactions per cycle was 8.34 %; the most common reaction was transient thrombocytopenia. ConclusionMost patients showed improvement in severity and decrease in corticosteroid dose and anti-BP180 antibody levels post-treatment, indicating that IVIG is useful for corticosteroid-unresponsive BP treatment.

070 Treating Bullous Pemphigoid by Inhibiting FcRn: A Phase 2/3 Trial with Efgartigimod

Efgartigimod (EFG) is an engineered Fc fragment that inhibits the activity of the neonatal Fc receptor (FcRn), thereby reducing the levels of circulating immunoglobulin G (IgG), including pathogenic IgG autoantibody, levels. EFG is clinically efficacious and generally well tolerated in phase 2 and 3 trials in multiple IgG-mediated disorders. Bullous pemphigoid (BP) is an autoimmune blistering disease, characterized by subepidermal blisters and mediated by IgG autoantibodies against BP180 (type XVII collagen) and BP230, structural proteins of the dermal-epidermal junction. Administration of an EFG analogue prior to and after that of pathogenic anti-BP180 IgG antibodies in a BP mouse model demonstrated efficacy in reducing skin disease activity. EFG will be evaluated as a therapy for BP in BALLAD, a phase 2/3 randomized, double-blinded, placebo-controlled trial (NCT05267600). BALLAD will be conducted in two parts – a proof-of-concept Part A (N=40) and a confirmatory Part B (N=120). Both parts are identical in schedule, structure, assessments, and conduct. 2000 mg EFG PH20 SC will be given on days 1 and 8, and 1000 mg EFG PH20 SC will be given weekly through week 35. Oral corticosteroids starting at 0.5 mg/kg/day of prednisone will be administered to the EFG PH20 SC and placebo PH20 SC groups and adjusted to each participant’s disease status. The primary endpoint is the proportion of participants in complete remission on minimal oral corticosteroid therapy (≤0.1 mg/kg/day) for ≥8 weeks at week 26. Key secondary endpoints include cumulative dose of oral corticosteroids from day 1 to week 36, change in the Bullous Pemphigoid Disease Area Index (BPDAI) score, incidence and severity of adverse events, and quality of life scores.

Dipeptidyl Peptidase-4 Inhibitor-Related Bullous Pemphigoid: Clinical, Laboratory, and Histological Features, and Possible Pathogenesis.

Dipeptidyl peptidase-4 inhibitor (DPP4i) is a widely used antidiabetic agent. Emerging cases of DPP4i-associated bullous pemphigoid (DBP), whose pathogenesis remains unclear, have been reported. Thus, a retrospective study was conducted from January 2016 to June 2021 to determine the clinical, laboratory, and histopathological features of DBP and idiopathic bullous pemphigoid (IBP). We set up in vitro experiments using vildagliptin-treated HaCaT keratinocytes to validate what we found by analyzing published RNA sequencing data about the genes related to the dermal-epidermal junction. We also observed IL-6 expression by HaCaT cells treated with vildagliptin. We enrolled 20 patients with DBP and 40 patients with IBP. The total Bullous Pemphigoid Disease Area Index (BPDAI) score was similar in both groups. However, the BPDAI score of erosions and blisters in DBP was significantly higher than that in IBP (24.6 vs. 16.68, p = 0.0189), and the score for urticaria and erythema was lower in DBP (12 vs. 19.05, p = 0.0183). The pathological features showed that the mean infiltrating eosinophil number per high-power field was significantly lower in DBP than in IBP (16.7 vs. 27.08, p = 0.023). The expression of LAMA3, LAMB3, LAMC2, DST, and COL17A1 decreased significantly in vildagliptin-treated human keratinocytes. On the other hand, IL-6, the hallmark cytokine of bullous pemphigoid (BP) severity, was found to be upregulated in HaCaT cells by vildagliptin. These experimental findings imply less of a requirement for eosinophil infiltration to drive the inflammatory cascades in DBP blistering. Both immunologic and non-immunologic pathways could be employed for the development of DBP. Our findings may help explain the higher incidence of non-inflammatory BP that was observed in DBP.

The effect of skin colour and Fitzpatrick skin type on Bullous Pemphigoid Disease Area Index (BPDAI) scores

The effect of skin colour and Fitzpatrick skin type on Bullous Pemphigoid Disease Area Index (BPDAI) scores

Clinical severity scores as a guide for prediction of initial treatment responses in pemphigus and pemphigoid patients.

Pemphigus and pemphigoid are autoimmune blistering diseases that affect mucosa and skin. Several clinical scoring systems, including the pemphigus disease area index (PDAI) and the bullous pemphigoid disease area index (BPDAI), have been validated for managing disease activity and severity. Current guidelines recommend that treatment response be evaluated with clinical scores and that additional second-line therapies be considered if initial treatment is insufficient for disease control. However, there have been few studies analyzing correlations between PDAI/BPDAI transitions and initial treatment effects. To investigate whether PDAI/BPDAI transitions during the treatment initiation phase correlate with initial treatment responses and whether such information can be used as a guide for necessary additional treatment, we retrospectively analyzed 67 pemphigus patients and 47 pemphigoid patients who received initial treatment at Keio University between 2012 and 2018. The clinical symptoms were evaluated weekly with PDAI/BPDAI. The patients were divided into two groups: in group A, disease was controlled only with oral corticosteroids and immunosuppressants (initial treatment), whereas in group B additional therapies were required due to insufficient responses. In pemphigus, the PDAI ratio of day 7/day 0 was significantly reduced in group A compared to group B (0.548 vs 0.761, P < 0.01) after initial treatment had started. In pemphigoid, the ratios of day 7/day 0 of BPDAI (erosion/blister) and BPDAI (urticaria/erythema) significantly decreased in group A compared to group B (0.565 vs 0.901 and 0.350 vs 0.760, respectively, P < 0.05). Receiver operating characteristic analyses on PDAI, BPDAI (erosion/blister) and BPDAI (urticaria/erythema) revealed that the cut-off values in the ratios of day 7/day 0 were 0.762, 0.675, and 0.568, respectively. Our results suggest that PDAI/BPDAI transitions during the initial phase of the treatments may be useful to predict the outcome of the treatment provided and the necessity of additional therapies to achieve disease control.

684 Variability in bullous pemphigoid disease area index scoring in patients of color

The Bullous Pemphigoid Disease Area Index (BPDAI) is an objective measure with activity scoring divided into erosions/blisters, erythema/urticaria, and damage. Emory Autoimmune Blistering Disease (AIBD) Clinic treats many patients with darker skin tones and the erythema/urticaria component can be challenging in patients with darker skin. In this study, we explored the effect of Race and Fitzpatrick skin type (FST) on BPDAI total activity score (BPDAI-TAS) and pruritus component scores (BPDAI-PCS) based on a retrospective chart review of BP patients from 2014 to 2020.

239 Incidence and severity of itch and pain in bullous pemphigoid

Itch is a common manifestation of Bullous Pemphigoid (BP) that may indicate blister onset or recurrence. Recent studies characterized the effect of itch on quality of life (QoL) in BP, though the literature regarding pain in BP is sparse. We compare itch and pain reported by patients diagnosed with BP. Data from the initial study visits of 38 subjects enrolled in our prospective blistering disease database was retrospectively reviewed. Bullous Pemphigoid Disease Area Index (BPDAI) activity scores, Physician Global Assessment (PGA) activity scores, and Patient Global Assessment (PtGA) itch and pain were completed at the study visit.

Dupilumab combined with low-dose systemic steroid therapy improves efficacy and safety for bullous pemphigoid.

Routine systemic therapy for bullous pemphigoid (BP) has been challenged due to the inevitably adverse effects. According to the successful applications of dupilumab in BP cases reported, therefore, we investigate the real-life efficacy and safety of dupilumab combined with low-dose oral steroid for BP. A cohort of BP patients who received either dupilumab plus low-dose methylprednisolone (dupilumab group) or merely methylprednisolone (control group) was retrospectively reviewed. The time to disease control was investigated. Additionally, the control dose and cumulative dosage of steroids, Bullous Pemphigoid Disease Area Index (BPDAI) scores, pruritus scores, and adverse events were assessed. A total of 40 patients, with 20 in each group, were retrospectively studied. The time to disease control was shorter in the dupilumab group than the control group (14 days vs. 19 days, p=0.043). When the disease was controlled, the control dose and cumulative dosage of methylprednisolone in the dupilumab group were substantially lower than those of the control (24.6mg vs. 48.8 mg, 376.8mg vs. 985.6 mg, both p < 0.01). Compared with the control, the percentage change from baseline in BPDAI scores and pruritus scores were both significantly reduced, and the adverse events were also less frequent in the dupilumab group. The combination therapy of dupilumab plus low-dose methylprednisolone exhibits superior efficacy and safety in comparison with the current first-line systemic therapy for BP.